How phenotype and developmental stage affect the genes we find: GABRA2 and impulsivity.
How phenotype and developmental stage affect the genes we find: GABRA2 and impulsivity.
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DOI：
10.1017/thg.2013.20
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发表时间：
2013-06
影响因子：
0.9
通讯作者：
Kramer, John
中科院分区：
文献类型：
--
作者：
Dick, Danielle M.;Aliev, Fazil;Latendresse, Shawn;Porjesz, Bernice;Schuckit, Marc;Rangaswamy, Madhavi;Hesselbrock, Victor;Edenberg, Howard;Nurnberger, John, Jr.;Agrawal, Arpana;Bierut, Laura;Wang, Jen;Bucholz, Kathy;Kuperman, Samuel;Kramer, John
众所周知，检测和复制与精神疾病有关的基因是非常困难的。表型测量作为一种解释，尽管大多数讨论集中在二元诊断的问题上。本文重点关注表型测量的两个额外组成部分，在评估遗传关联时值得进一步考虑：(1)用于反映感兴趣结果的测量，以及(2)研究人群的发育阶段。我们围绕冲动性和外化障碍的构建，以及这些措施与特定基因GABRA2的关联，集中讨论这些问题。数据分析来自酒精中毒遗传学合作研究第四阶段评估青少年和年轻人（12-26岁；N = 2128）。采用精神病学访谈法测量酒精依赖、非法药物依赖、儿童行为障碍和成人反社会人格障碍症状；Achenbach青少年/成人自我报告外化量表；朱克曼寻求刺激量表；Barratt冲动性量表；NEO外向性和意识。GABRA2与亚临床水平的外化行为有关，这是由Achenbach在青少年和年轻成人样本中测量的。与先前在成人样本中的关联相反，在这些年轻样本中，它与任何外部性疾病的临床水平DSM症状计数无关。这也与寻求感觉和外向性有关，但仅限于青少年样本。与Barratt冲动性量表或尽责性没有关联。我们的研究结果表明，GABRA2最初赋予最终酒精问题风险的途径始于青少年早期寻求感觉的倾向。研究结果支持了冲动性的异质性，并证明了用于评估兴趣结构和参与者年龄的测量方法对检测遗传关联具有深远的意义。
The detection and replication of genes involved in psychiatric outcome has been notoriously difficult. Phenotypic measurement has been offered as one explanation, although most of this discussion has focused on problems with binary diagnoses. This article focuses on two additional components of phenotypic measurement that deserve further consideration in evaluating genetic associations: (1) the measure used to reflect the outcome of interest, and (2) the developmental stage of the study population. We focus our discussion of these issues around the construct of impulsivity and externalizing disorders, and the association of these measures with a specific gene, GABRA2. Data were analyzed from the Collaborative Study on the Genetics of Alcoholism Phase IV assessment of adolescents and young adults (ages 12–26; N = 2,128). Alcohol dependence, illicit drug dependence, childhood conduct disorder, and adult antisocial personality disorder symptoms were measured by psychiatric interview; Achenbach youth/adult self-report externalizing scale; Zuckerman Sensation-Seeking scale; Barratt Impulsivity scale; NEO extraversion and consciousness. GABRA2 was associated with subclinical levels of externalizing behavior as measured by the Achenbach in both the adolescent and young adult samples. Contrary to previous associations in adult samples, it was not associated with clinical-level DSM symptom counts of any externalizing disorders in these younger samples. There was also association with sensation-seeking and extraversion, but only in the adolescent sample. There was no association with the Barratt impulsivity scale or conscientiousness. Our results suggest that the pathway by which GABRA2 initially confers risk for eventual alcohol problems begins with a predisposition to sensation-seeking early in adolescence. The findings support the heterogeneous nature of impulsivity and demonstrate that both the measure used to assess a construct of interest and the age of the participants can have profound implications for the detection of genetic associations.
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影响因子：
3.4
作者：
Dick DM;Smith G;Olausson P;Mitchell SH;Leeman RF;O'Malley SS;Sher K
通讯作者：
Sher K
影响因子：
9.8
作者：
Edenberg, HJ;Dick, DM;Begleiter, H
通讯作者：
Begleiter, H
影响因子：
6.4
作者：
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通讯作者：
Dick, Danielle M.
DOI：
10.1002/ajmg.b.30091
发表时间：
2004-08-15
影响因子：
2.8
作者：
Covault, J;Gelernter, J;Kranzler, HR
通讯作者：
Kranzler, HR
DOI：
10.1002/ajmg.b.30336
发表时间：
2006-09-05
影响因子：
2.8
作者：
Enoch, Mary-Anne;Schwartz, Lori;Goldman, David
通讯作者：
Goldman, David